As an administration method of a drug, conventionally oral administration methods which use tablets, capsules and syrups are known; in recent years however, drug-administration methods using adhesive patches have been investigated. With a method using adhesive patches, various problems involved in oral administration methods are solved, and the method has several advantages including a reduction of the number of administrations, improvement in compliance, and easiness of administration and its discontinuation; therefore, it has been expected as an useful drug administration method for elderly and child patients.
However, when a conventional adhesive patch is used, because the cornified layer has extremely high fat solubility and low skin permeability of a drug in general, and the cornified layer of the normal skin has a barrier function to prevent invasion of foreign matters, in many cases a blended drug is not percutaneously absorbed sufficiently.
Therefore, to increase the skin absorbability of a drug in percutaneous administration using adhesive patches, various studies on composition, etc. of adhesive agents used in the adhesive patches have been carried out and, as a part of such studies, adhesive patches which use polymer materials such as an acrylic polymer or rubber polymer as an adhesive base have been proposed (refer to patent documents 1-6). However, even with these attempts, the skin absorbability of a drug blended in an adhesive patch is not sufficient, and further development of preparations having superior skin absorbability has been desired. In addition, preparations produced with conventional adhesive bases sometimes cause problems of skin irritation and aging instability of a drug blended in the adhesive patch, which leads to expectation of further improvement in terms of preparation.
Meanwhile, ambroxol, in particular ambroxol hydrochloride is known as an excellent expectrant, and is widely used in clinical practices for respiratory diseases in which severe expectration is often observed. Conventionally, oral administration methods using tablets, liquid agents, syrups, dry syrups, and capsules have been widely adopted; however, decomposition and metabolism accompanying with oral administration cannot be avoided. In addition, expectration is known to become severe at the time of awakening early; accordingly, it is important for an expectrant to be effective in early morning than during daytime. Nonetheless, because ambroxol has a short half life inside the body, if it is administered via a conventional oral administration method (tablet, syrup, etc.) after supper, sufficient blood concentration of ambroxol would not be obtained in early morning, resulting in insufficient exertion of the drug efficacy.
To solve such problems, sustained-release capsules have been developed, making it possible to maintain a high blood concentration continuously and to exert superior therapeutic effects compared with tablets, etc. However, it is still difficult for preparations other than sustained-release capsules to perform effective therapy; even sustained-release capsules have a disadvantage in terms of convenience of administration. That is, 70% of patients prescribed with an expectrant are children and the elderly, and considering the swallowing difficulty of the elderly and body type of children, capsule dosage form is a difficult one for such patients to take. In addition, in the recent aging society, the number of elderly patients with decreased swallowing ability is increasing; thus, a preparation having a dosage form that is easy to take has been clinically desired.
In patent documents 7-9, tape preparations, adhesive agents and adhesive tapes for medical use are disclosed, in which ambroxol hydrochloride is described as a drug that may be used therein. However, in these documents, the name of ambroxol hydrochloride is only just mentioned without any specific formula, and therefore the disclosure in these documents is not sufficient from the practical viewpoint; whether or not an adhesive patch containing ambroxol hydrochloride as an effective preparation, that has sufficient skin absorbability to be used for actual therapy of patients, can be produced has not yet been clarified.
Furthermore, as an external preparation of expectrant, a skin-absorption preparation containing bromhexine as an active component has been disclosed (patent document 10); however, a skin-absorption preparation containing ambroxol has not yet existed.    Patent document 1: JP, A, 4-266821    Patent document 2: JP, A, 9-301854    Patent document 3: WO2002/069942    Patent document 4: WO2004/019930    Patent document 5: WO2004/019987    Patent document 6: WO2004/019988    Patent document 7: JP No. 3132837    Patent document 8: JP No. 3192765    Patent document 9: JP No. 3233732    Patent document 10: JP, A, 11-12167